We shall define specific relationships among BMC, calcium intake and estrogen levels in women runners. Because of the wide prevalence of "athletic amenorrhea" and the relationship between hypoestrogenemia and diminution of BMC, we believe that detailed studies of the relationship among exercise training, circulating levels of estrogens, calcium intake and BMC are of major significance. Moreover, since the available literature is dominated by cross- sectional and retrospective observations which have not addressed testable or mechanistic hypotheses, we believe there is a critical need to acquire more refined insights into descrete endocrine pathogenic mechanisms that influence the gonadotropin-steroid axis and relate these mechanisms to changes in BMC. We also believe there is a critical need to determine the relationship between circulating levels of estrogens, calcium intake and BMC prospectively. We will study eumenorrheic, oligomenorrheic and amenorrheic women who run at least 25 miles/week. One half will be randomly assigned to a calcium supplementation group; the remaining to a placebo group. Subjects will maintain their regular training patterns and will be followed for 3 years. A non-running, eumenorrheic group will serve as non-exercising controls. Our objectives are: to search for endocrine alterations in the menstrual cycle; to relate them to diminution of BMC; and to determine whether the effectiveness of calcium supplementation with respect to BMC is related to circulating levels of estrogens. We will also undertake a three-year prospective endurance training program designed to prepare initially untrained, eumenorrheic women to run the equivalent of a marathon. Women will be subjected to serial examinations of fitness levels, dietary intake, reproductive hormone status and BMC to allow us to observe prospectively changes in menstrual cyclicity as a result of initiating a training program and relate those changes to changes in BMC. These data will permit individual women and their physicians to better understand the impact and reversibility of exercise-induced alterations in menstrual cyclicity and BMC and provide insights into the mechanisms underlying bone loss in women athletes. These data may foster new approaches to the treatment of premature bone loss.